Synthesis and bioevaluation of diarylpyrazoles as antiproliferative agents

Two series of diarylpyrazoles were designed as potential microtubule targeting agents. Twenty-eight target compounds were synthesized and exhibited potent antiproliferative activity. Compound 15e, displayed potent antiproliferative activity against SGC-7901, KB and HT-1080 cell lines, respectively, and was comparable to the positive control, CA-4. Tubulin polymerization experiments indicated that 15e effectively inhibited the tubulin polymerization, and immunostaining assay revealed that it significantly disrupted tubulin microtubule dynamics. Moreover, cell cycle studies revealed that compound 15e dramatically arrested cell cycle progression at G2/M phase and caused microtubule destabilization. Molecular modeling studies showed that 15e could bind to the colchicine binding site on microtubules.